title: The structure of the human ALL-1/MLL/HRX gene.
abstract: The human ALL-1/MLL/HRX gene on chromosome 11q23 is the site of many locally clustered chromosomal alterations associated with several types of acute leukemias, including deletions. partial duplications and reciprocal translocations. Structurally variant proteins derived from an altered ALL-1 gene presumably make essential contributions to the malignant transformation of hematopoietic progenitor cells. The ALL-1 gene is spread over approximately 92 kb and consists of at least 37 exons. An exon/intron map including the position of the 3'-end of the gene and a detailed restriction map were produced and an updated map is presented. Data from other laboratories were incorporated where compatible. Exon/intron boundaries were sequenced and an intron-phase analysis was performed. The results are expected to contribute to a better understanding of those structural alterations of the gene that conserve the open reading frame and produce presumably oncogenic variants of the ALL-1 protein. They will also facilitate the rapid molecular diagnosis of structural alterations of this gene and the choice of therapeutic options. Mechanisms that may potentially account for the striking clustering of the translocation breakpoints in the breakpoint cluster region of the gene are discussed.
authors.affiliation: Department of Genetics, University of Erlangen-Nürnberg, Erlangen, Germany. rmarscha@biologie.uni-erlangen.de
authors.forename: R
authors.initials: R
authors.lastname: Marschalek
authors.forename: I
authors.initials: I
authors.lastname: Nilson
authors.forename: K
authors.initials: K
authors.lastname: Löchner
authors.forename: R
authors.initials: R
authors.lastname: Greim
authors.forename: G
authors.initials: G
authors.lastname: Siegler
authors.forename: J
authors.initials: J
authors.lastname: Greil
authors.forename: J D
authors.initials: JD
authors.lastname: Beck
authors.forename: G H
authors.initials: GH
authors.lastname: Fey
mesh_terms: D001483:Base Sequence; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005091:Exons / Q000235:genetics; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D007438:Introns / Q000235:genetics; D007938:Leukemia / Q000235:genetics*; D008969:Molecular Sequence Data; D051788:Myeloid-Lymphoid Leukemia Protein; D009363:Neoplasm Proteins / Q000235:genetics*; D009857:Oncogenes / Q000235:genetics*; D011519:Proto-Oncogenes; D012091:Repetitive Sequences, Nucleic Acid; D015183:Restriction Mapping; D016415:Sequence Alignment; D014157:Transcription Factors; D014178:Translocation, Genetic
chemical_list: D004268:DNA-Binding Proteins; C497422:KMT2A protein, human; D009363:Neoplasm Proteins; D014157:Transcription Factors; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase